Klotho knock-out mice are an important model for vascular calcification, which is associated with chronic kidney disease. In chronic kidney disease, serum magnesium inversely correlates with vascular calcification. Here we determine the effects of serum magnesium on aortic calcification in Klotho knock-out mice treated with a minimal or a high magnesium diet from birth. After eight weeks, serum biochemistry and aorta and bone tissues were studied. Protective effects of magnesium were characterized by RNA-sequencing of the aorta and micro-CT analysis was performed to study bone integrity. A high magnesium diet prevented vascular calcification and aortic gene expression of Runx2 and matrix Gla protein found in such mice on the minimal magnesium diet. Differential expression of inflammation and extracellular matrix remodeling genes accompanied the beneficial effects of magnesium on calcification. High dietary magnesium did not affect serum parathyroid hormone, 1,25-dihydroxyvitamin D3 or calcium. High magnesium intake prevented vascular calcification despite increased fibroblast growth factor-23 and phosphate concentration in the knock-out mice. Compared to mice on the minimal magnesium diet, the high magnesium diet reduced femoral bone mineral density by 20% and caused excessive osteoid formation indicating osteomalacia. Osteoclast activity was unaffected by the high magnesium diet. In Saos-2 osteoblasts, magnesium supplementation reduced mineralization independent of osteoblast function. Thus, high dietary magnesium prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways within the aorta. Hence magnesium treatment may be promising to prevent vascular calcification, but the risk for osteomalacia should be considered.

中文翻译：

---

镁可防止 Klotho 缺乏症中的血管钙化。

Klotho 基因敲除小鼠是血管钙化的重要模型，与慢性肾病有关。在慢性肾病中，血清镁与血管钙化呈负相关。在这里，我们确定血清镁对 Klotho 基因敲除小鼠的主动脉钙化的影响，这些小鼠从出生时就接受了最低或高镁饮食。八周后，研究了血清生化和主动脉和骨组织。镁的保护作用通过主动脉的 RNA 测序来表征，并进行微 CT 分析以研究骨骼完整性。高镁饮食可防止在此类小鼠中发现的低镁饮食的血管钙化和 Runx2 和基质 Gla 蛋白的主动脉基因表达。炎症和细胞外基质重塑基因的差异表达伴随着镁对钙化的有益作用。高膳食镁不影响血清甲状旁腺激素、1,25-二羟基维生素 D3 或钙。尽管敲除小鼠体内的成纤维细胞生长因子 23 和磷酸盐浓度增加，但高镁摄入量可防止血管钙化。与最低镁饮食的小鼠相比，高镁饮食使股骨矿物质密度降低了 20%，并导致过度的类骨质形成，表明骨软化症。破骨细胞活性不受高镁饮食的影响。在 Saos-2 成骨细胞中，镁补充剂减少了与成骨细胞功能无关的矿化。因此，高膳食镁可防止 Klotho 基因敲除小鼠的钙化。这些作用可能是通过减少主动脉内的炎症和细胞外基质重塑途径来介导的。因此，镁治疗可能有望预防血管钙化，但应考虑骨软化的风险。